Case report BMJ Case Rep: first published as 10.1136/bcr-2021-242325 on 22 July 2021. Downloaded from Case of acute kidney injury due to bilimbi fruit ingestion Koh-Wei­ Wong,1 Meryl Grace Lansing2

1Department of Medicine, SUMMARY evidence of obstructive uropathy. He was started on Hospital Queen Elizabeth, Kota Bilimbi fruit is widely eaten in . Rarely reported amlodipine 5 mg daily for his hypertension. Further Kinabalu, Sabah, Malaysia investigations were antistreptolysin-­O titre which 2 is its potential to cause acute kidney injury (AKI) in Medical Based Department, patients with prior normal renal function. The possible was negative; both C3 and C4 were raised; antinu- Universiti Malaysia Sabah, Kota dangers of its consumption are still relatively unknown clear antibodies were negative; hepatitis B surface Kinabalu, Sabah, Malaysia among many. This case highlights the importance of antigen and hepatitis antibody (anti-­hepatitis C virus) were non-­reactive. Since admission, his Correspondence to taking a thorough dietary history in patients with AKI. Dr Meryl Grace Lansing; We also hope to increase awareness among healthcare serial serum creatinine levels were in a decreasing meryl.​ ​lansing@ums.​ ​edu.my​ professionals on the nephrotoxic and neurotoxic effects pattern—633 µmol/L (day 1), 442 µmol/L (day of bilimbi fruits. 2), 401.8 µmol/L (day 3), 368.5 µmol/L (day 4), Accepted 6 July 2021 331.3 µmol/L (day 5), 315.2 µmol/L (day 6). He was discharged on day 6 in view of his improving kidney function. BACKGROUND Bilimbi fruit ( bilimbi), otherwise known as ‘belimbing buluh’ in Malay and ‘tulod ulod’ in OUTCOME AND FOLLOW-UP Dusun, is a popular tropical fruit. The fruit is sour On outpatient review, his renal function slowly and has a characteristic cylindrical shape. Bilimbi improved. Three weeks later, he reported dizziness fruit can be eaten raw, cooked or pickled. Bilimbi with the amlodipine, and he stopped taking it. His fruit is often considered a medicinal fruit and used blood pressure without the medication on review to treat various ailments such as cough and rheu- was 134 mm Hg (systolic) and 94 mm Hg (diastolic). matism. However, the fruit contains high oxalic His creatinine continued to improve to 169 µmol/L acid levels and may become nephrotoxic when (day 11), 99.05 µmol/L (at 6 weeks), 107.63 µmol/L 1 consumed in large quantity,. Over the years, there (at 10 weeks), 76.76 µmol/L (at 8 months). have been case reports from tropical countries documenting its neurotoxicity and nephrotox- icity among patients with chronic kidney disease DISCUSSION http://casereports.bmj.com/ (CKD).2 Rarely reported, it may also cause acute Although bilimbi fruit is widely consumed in kidney injury (AKI) in people with normal renal Malaysia, AKI due to Averrhoa bilimbi is rare, and function. Here we present a case of AKI after the case reports documenting its toxicity are scarce. Its ingestion of bilimbi fruit. nephrotoxicity is due to crystal deposition resulting in acute oxalate nephropathy, affecting people with normal kidney function, but more CASE REPORT frequently in those with renal dysfunction.2 Bakul A- 34-­year old­ man who is a smoker, with no signif- et al from reported a series of cases in icant medical or surgical history, presented with a where 10 patients developed AKI following inges-

5-day­ history of abdominal pain and diarrhoea. He tion of bilimbi fruit juice where 7 out of 10 required on October 1, 2021 by guest. Protected copyright. has no family history of renal diseases. The colicky haemodialysis.3 Nair et al also reported two cases of abdominal pain started at the left iliac fossa radi- acute renal injury after both patients took bilimbi ating to the back and the whole of the abdomen. fruit juice as a presumed treatment for dyslipi- One day before the onset of the abdominal pain, daemia.4 The renal biopsy findings from patients he consumed about 1 kg of bilimbi fruits (about who developed AKI following bilimbi fruit inges- 40 fruits). He was afebrile on presentation, and tion showed acute tubulointerstitial nephritis and his blood pressure was 158 mm Hg (systolic) and tubular obstruction with calcium oxalate deposits. 101 mm Hg (diastolic). Abdominal examination It is believed that the nephrotoxicity comes from revealed mild tenderness over the lower umbilical the direct tubular damage from the calcium oxalate © BMJ Publishing Group region, and he had no pedal oedema. Cardiovas- crystal obstruction of the tubules. Other mecha- Limited 2021. Re-­use cular and respiratory examinations were normal. nisms such as oxidative stress causing direct renal permitted under CC BY-­NC. No His urine output remained good. commercial re-use­ . See rights cytotoxic effects and apoptosis, indirect renal and permissions. Published cytotoxic effects and necroinflammation from the by BMJ. INVESTIGATIONS crystals, and impairment of intracellular calcium Biochemical investigations revealed a serum creat- homeostasis may also account for the severity and To cite: Wong K-W,­ 5 Lansing MG. BMJ Case inine of 633.89 µmol/L, potassium of 3.9 mmol/L extent of renal damage. Consideration of other Rep 2021;14:e242325. and urea of 10.1 mmol/L. His urinalysis was factors predisposing to AKI, such as the role of doi:10.1136/bcr-2021- normal, with no proteinuria or microscopic haema- genetic and epigenetic and the effects of pre-­existing 242325 turia. Ultrasonography of his abdomen showed no comorbidities, may aid in further understanding of

Wong K-­W, Lansing MG. BMJ Case Rep 2021;14:e242325. doi:10.1136/bcr-2021-242325 1 Case report BMJ Case Rep: first published as 10.1136/bcr-2021-242325 on 22 July 2021. Downloaded from the mechanisms involved in AKI secondary to dietary oxalate. known. AKI may occur in patients with prior normal renal func- Although the exact amount of bilimbi fruit ingestion (either the tion following ingestion of bilimbi fruit, especially when taken fruit or the fruit juice) that may cause toxicity is not determined, in large quantity. Therefore, efforts must be made to ensure that ingestion of a large number of fruits or its juice or ingestion on healthcare professionals are aware of its potential neurotox- an empty stomach seems to be the risk factor. Magnesium and icity and nephrotoxicity. This case highlights the importance of calcium ions in food bind to oxalate in the gastrointestinal tract, a thorough dietary history in patients with AKI. Patients with thus preventing oxalate absorption. Ingestion of bilimbi fruit CKD, especially those in the advanced stage, should be advised on an empty stomach may result in increased oxalate absorp- against eating bilimbi fruits. tion, leading to AKI. Some patients (such as ours here) may not require dialysis, but others may need haemodialysis or haemo- Learning points perfusion. Peritoneal dialysis was reported to be ineffective in the presence of neurological manifestations. ►► A thorough dietary history should be included in all patients Averrhoa bilimbi and Averrhoa (starfruit) belong with acute kidney injury. to the family and share similar biochemical prop- ►► Healthcare professionals should be aware of the potential erties.6 There are many reported cases of star fruit-induced­ neurotoxic and nephrotoxic effects of bilimbi fruits. oxalate nephrotoxicity in those with existing renal impairment. ►► Patients with chronic kidney disease, especially those in the However, the oxalic acid content in star fruit is less than bilimbi advanced stage, should be advised against eating bilimbi (0.8–7.3 mg/g).1 Simon et al reported a case of an elderly woman fruits. with CKD on dialysis who presented with intractable hiccups and altered sensorium following ingestion of both bilimbi and star fruit. The convincing time relationship between the inges- Acknowledgements The authors would like to thank the Director General of tion of these fruits and the onset of symptoms in this case Health Malaysia for the permission to publish this paper. strongly suggests caramboxin intoxication.2 In 2017, Caetano Contributors K-­WW—data collection and writing the main content of the case et al described the case of a patient with CKD on dialysis who report. MGL—editing and writing the summary, background and parts of the discussion. developed neurological symptoms after the ingestion of bilimbi fruit, similar to those related to star fruit ingestion.6 Initially, Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-­for-­profit sectors. it was thought the neurotoxicity was due to the high oxalate content of the fruit, but recent findings seem to suggest another Competing interests None declared. neurotoxin, called caramboxin, as the responsible agent. Caram- Patient consent for publication Obtained. boxin is an amino acid analogue and is metabolised and excreted Provenance and peer review Not commissioned; externally peer reviewed. by the kidneys. Caramboxin has an excitatory, seizure-causing­ Open access This is an open access article distributed in accordance with the and neurodegenerative action. The neurotoxic effects of caram- Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which boxin may be mediated by increased excitation (due to activation permits others to distribute, remix, adapt, build upon this work non-­commercially, of NMDA, AMPA and kainate receptors) or decreased inhibition and license their derivative works on different terms, provided the original work is properly cited and the use is non-­commercial. See: http://​creativecommons.​org/​ (due to decreased GABA binding). In patients with normal renal http://casereports.bmj.com/ licenses/by-​ ​nc/4.​ ​0/. function, the neurotoxin is absorbed, distributed and excreted by the kidneys. In patients with CKD, the neurotoxin cannot be eliminated effectively by the kidneys, and its toxic effect may be REFERENCES fatal. The neurological symptoms of hiccups, vomiting, mental 1 LIMA VLAGDE, MÉLO EDEA, SANTOS LIMA LDOS. Physicochemical characteristics of confusion, agitation and seizures in a patient with end-­stage BILIMBI (Averrhoa bilimbi L.). Rev Bras Frutic 2001;23:421–3. renal disease may be confused by other differential diagnoses 2 Simon S, Thomas J, Jayaram V. Status epilepticus owing to consumption of seasonal fruit in dialysis: case report. J Clin Nephrol Ren Care;6:055. such as uraemic encephalopathy and meningoencephalitis. The 3 Bakul G, Unni VN, Seethaleksmy NV, et al. Acute oxalate nephropathy due to ’Averrhoa symptoms are known to occur within hours of ingestion; thus, bilimbi’ fruit juice ingestion. Indian J Nephrol 2013;23:297–300. a history of ingestion of the fruit may be the most crucial clue 4 Nair S, George J, Kumar S, et al. Acute oxalate nephropathy following ingestion of to the diagnosis in an acute setting. Caramboxin is water soluble Averrhoa bilimbi juice. Case Rep Nephrol 2014;2014:240936. on October 1, 2021 by guest. Protected copyright. and dialysable, and therefore intense dialysis may improve the 5 Yasawardene P, Jayarajah U, De Zoysa I, et al. Mechanisms of StAR fruit () toxicity: a mini-­review. Toxicon 2020;187:198–202. outcome. 6 Caetano CP, de Sá CB, Faleiros BAP, et al. Neurotoxicity following the Ingestion of Despite their popularity, the potential harms of the tropical Bilimbi Fruit (Averrhoa bilimbi) in an End-Stage­ Renal Disease Patient on Hemodialysis. fruit bilimbi, and its close relative, the starfruit, are not well Case Rep Nephrol Dial 2017;7:6–12.

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2 Wong K-W,­ Lansing MG. BMJ Case Rep 2021;14:e242325. doi:10.1136/bcr-2021-242325